Efficacy of Three Regimens of Chloroquine and Primaquine for the Treatment of Plasmodium Vivax Malaria in Cruzeiro do Sul, Acre, Brazil
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 257
- 试验地点
- 1
- 主要终点
- Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled
研究概览
简要总结
We plan to assess the efficacy of 3 different regimens of chloroquine and primaquine for the treatment of P. vivax infections in Cruzeiro do Sul, Acre, Brazil. Patients will be divided in 3 different groups: treatment with regular dose of primaquine (0.5 mg/kg per day for 7 days) with directly observed therapy; regular dose of primaquine without directly observed therapy; and increased total dose of primaquine (0.5 mg/kg per day for14 days) with directly observed therapy. All patients will receive chloroquine (CQ) for three days at a daily dose of approximately 25 mg/Kg in accordance with the Brazilian National Malaria Control guidelines. Clinical and parasitologic parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy and for a total period of 168 days (24 weeks) to evaluate chances of recrudescence, relapse, or reinfection. Results from this drug efficacy study will be used to assist the Brazilian Ministry of Health in assessing their national malaria treatment policy for P. vivax malaria.
详细描述
Background: The World Health Organization recommends that antimalarial treatment policies be evaluated every few years to check their efficacy. P. vivax malaria is the most common species in Brazil and cases are concentrated in the Amazon Region in Brazil.
Objectives: Assess the efficacy of 3 different regimens of chloroquine and primaquine for the treatment of P. vivax infections in Cruzeiro do Sul, Acre, Brazil.
Methods: An in vivo drug efficacy study will be conducted in Cruzeiro do Sul, Acre State, Brazil. A total of 257 study participants ≥5 years of age with parasitologically confirmed P. vivax monoinfections will be included. Patients will be divided in 3 different groups: treatment with regular dose of primaquine (0.5 mg/kg per day for 7 days) with directly observed therapy; regular dose of primaquine without directly observed therapy; and increased total dose of primaquine (0.5 mg/kg per day for14 days) with directly observed therapy. All patients will receive chloroquine (CQ) for three days at a daily dose of approximately 25 mg/Kg in accordance with the Brazilian National Malaria Control guidelines. Primaquine will be given for 7 or 14 days under supervision or not, depending on the study group. Clinical and parasitologic parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy and for a total period of 168 days (24 weeks) to evaluate chances of recrudescence, relapse, or reinfection. Blood samples will be taken to measure the CQ levels in blood on Day 7 and day of failure, if occurring in the initial 28 days of follow up. In addition, a blood sample will be collected on filter paper on first day and on day of suspected failure to help differentiate parasite genotypes using techniques based on polymerase chain reaction. Results from this drug efficacy study will be used to assist the Brazilian Ministry of Health in assessing their national malaria treatment policy for P. vivax malaria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥5 years
- •Body weight <120 kg
- •Documented fever (axillary temperature ≥37.5o C) or history of fever during the previous 48 hours in the absence of another obvious cause of fever, such as pneumonia, otitis media, etc
- •Monoinfection with P. vivax with parasitemia between 100 and 200,000 asexual parasites/µl as determined by microscopic examination of thick and thin peripheral blood smears
- •Informed consent from the patient or parent/guardian (for those <18 years), assent from child (ages 7 to 17 years inclusive), patients 5 through 6 years old will not need an assent
- •Willingness on the part of the patient to return to the clinic and/or receive home visits for regular check-ups during the 24-week (168 days) follow-up period
- •Place of residence within 30-45 minutes of study site.
排除标准
- •Presence of malaria danger signs
- •Unable to drink
- •Vomiting (more than twice in the previous 24 hours)
- •Recent history of convulsions (one or more in the previous 24 hours)
- •Impaired consciousness
- •Unable to sit or stand
- •Presence of signs of severe malaria (WHO criteria)
- •Cerebral malaria (unarousable coma)
- •Severe anemia (hematocrit <15% or clinical signs) hemoglobin <5 mg/ml) (Note: we will use hemoglobin less than 8 mg/ml as exclusion criteria)
- •Renal failure (serum creatinine >3 mg/dL or clinical signs)
- •Pulmonary edema
- •Hypoglycemia (blood glucose <40mg/dL or clinical signs)
- •Shock (systolic blood pressure <70 mm Hg in adults; 50 mm Hg in children)
- •Spontaneous bleeding/disseminate intravascular coagulation
- •Repeated generalized convulsions
- •Acidemia/acidosis (clinical signs)
- •Macroscopic hemoglobinuria
- •Self-reported presence of other underlying chronic or severe diseases (e.g., cardiac, renal, hepatic diseases, HIV/AIDS, tuberculosis, malnutrition, psoriasis)
- •History of hypersensitivity reactions to any of the drugs being tested. Mild itching with CQ is not in itself a criterion for exclusion. This occurrence will be evaluated by the study doctor before excluding the patient for this reason alone.
- •Use of drugs with antimalarial activity in the past 30 days. (Annex D)
- •Current pregnancy (either self-reported being pregnant at enrollment or a positive urine or plasma pregnancy test at time of enrollment), previous pregnancy is not an exclusion criteria
- •Hemoglobin <8 mg/mL
- •G6PD deficiency. This will be a late exclusion criteria as soon as the results of G6PD testing becomes available.
研究组 & 干预措施
Primaquine Regular Dose Unsupervised
This is the regular primaquine dose Brazil without directly observed therapy.
干预措施: Primaquine (Drug)
Primaquine Regular Dose Supervised
This is the regular primaquine dose in Brazil but with directly observed therapy.
干预措施: Primaquine (Drug)
Primaquine Double Dose Unsupervised
This is the double total primaquine dose (14 days) in Brazil with directly observed therapy.
干预措施: Primaquine (Drug)
结局指标
主要结局
Participants With Adequate Clinical and Parasitologic Response Among Patients Enrolled
时间窗: 168 days
Participants with adequate clinical and parasitologic response among patients enrolled, meaning patients who did not fail treatment by day 168. Those are participants who at day 168 did not present clinical deterioration or presence of parasitemia.
次要结局
- Participants With Adequate Clinical and Parasitologic Response Based on Microsatellite-corrected Analysis Per Protocol Day 168(168 days)